Uimonen Katri, Merikallio Heta, Pääkkö Paavo, Harju Terttu, Mannermaa Arto, Palvimo Jorma, Kosma Veli-Matti, Soini Ylermi
Institute of Clinical Medicine, Department of Clinical Pathology and Forensic Medicine, University of Eastern Finland, Cancer Center of Eastern Finland, and Imaging Center, Department of Clinical pathology, Kuopio University Hospital, Kuopio, Finland.
Institute of Clinical Medicine, Department of Internal Medicine, Respiratory Unit, Centre of Excellence in Research, University of Oulu, Oulu, Finland.
Histol Histopathol. 2014 Jun;29(6):797-804. doi: 10.14670/HH-29.797. Epub 2013 Dec 27.
GASC1 (gene amplified in squamous cell carcinoma 1) encodes a nuclear protein that epigenetically catalyses the lysine demethylation of histones. We investigated the expression of GASC1 in different histological subtypes of lung cancer (n=289). Percentage value of GASC1 immunohistochemical expression was evaluated separately in the nuclei and cytoplasms of epithelial cancer cells. The results were compared with clinicopathologic factors and the smoking history of the patients. In lung tumor cells, 38% of nuclei and 54% of the cytoplasms stained positive for GASC1. Adenocarcinomas expressed more GASC1 nuclear (p=0.00011) and cytoplasmic (p=0.00074) positivity than squamous cell carcinoma. Smokers displayed less nuclear and cytoplasmic GASC1 expression than non-smokers (p=0.028 and p=0.036, respectively). Similarly, patients with more cytoplasmic positive staining had fewer pack years (p=0.043). Nuclear GASC1 expression had an impairing effect on survival when all histological lung cancer types were analysed together (p=0.039) and separately in squamous cell lung carcinoma (p=0.016). The results reveal that GASC1 expression is higher in adenocarcinoma than squamous cell carcinoma. Smoking decreases GASC1 expression in tumor cells, indicating that tobacco smoke may influence the methylation of histone 3 lysine residues in lung cancer. Nonetheless, nuclear GASC1 predicts a poor prognosis, especially in squamous cell carcinoma.
GASC1（鳞状细胞癌中扩增的基因1）编码一种核蛋白，该蛋白可通过表观遗传方式催化组蛋白的赖氨酸去甲基化。我们调查了GASC1在不同组织学亚型肺癌（n = 289）中的表达情况。分别在上皮癌细胞的细胞核和细胞质中评估GASC1免疫组化表达的百分比值。将结果与临床病理因素及患者的吸烟史进行比较。在肺肿瘤细胞中，38%的细胞核和54%的细胞质GASC1染色呈阳性。腺癌的GASC1细胞核（p = 0.00011）和细胞质（p = 0.00074）阳性表达比鳞状细胞癌更多。吸烟者的细胞核和细胞质GASC1表达低于不吸烟者（分别为p = 0.028和p = 0.036）。同样，细胞质阳性染色更多的患者吸烟包年数更少（p = 0.043）。当对所有组织学类型的肺癌一起分析时（p = 0.039）以及单独在肺鳞状细胞癌中分析时（p = 0.016），细胞核GASC1表达对生存有不利影响。结果显示，腺癌中GASC1的表达高于鳞状细胞癌。吸烟会降低肿瘤细胞中GASC1的表达，表明烟草烟雾可能影响肺癌中组蛋白3赖氨酸残基的甲基化。尽管如此，细胞核GASC1预示预后不良，尤其是在鳞状细胞癌中。
